After a change in the rate of ATP utilization by intact muscle, its rate of O2 consumption (QO2) follows with first order kinetics. I have recently shown that during such transients, QO2 increases in proportion to the decrease in creatine phosphate (CP), or equivalently, to the increase in creatine (Cr); the proportionality constant is (1/Taup), where Tau is the time constant of QO2 and p is the P:O2 ratio. These relationships will be used to quantitatively test two current competing models of respiratory control: that of Chance and co-workers, which postulates control via cytoplasmic [ADP]; and the "Cr-CP shuttle" model, which postulates that delivery of ADP to the mitochondrial matrix occurs via mitochondrial creatine kinase, under control by cytoplasmic [Cr] and [CP]. The DeltaQO2 caused by a given change in [Cr] and [CP] will be determined for mitochondria isolated from frog skeletal muscle and rabbit heart; the corresponding in vivo QO2 will be determined from measurement of mitochondrial markers both in vivo and in vitro. The shuttle model is correct only if this [Cr]-QO2 dose response curve matches the [Cr]-QO2 proportionality of intact muscle. The "ADP trigger" model has been solved to yield formal predicted transients in QO2 and the predicted [Cr]-QO2 relationship. The predictions for frog skeletal muscle will be hardened by measurement of KM-ADP, Qmax, [ADP]o, and Keq-CK. The model is valid only if it predicts the first order kinetics of QO2 (Tau = 2.6 min) and the [Cr]-QO2 proportionality actually observed when the QO2 of isolated mitochondria is at its inherent maximum (saturating ADP, Pi, and O2), the increase in [ADP] from its basal level is equivalent or equal to 100MuM, a change large enough to be measured if it occurred in vivo. The non-O2-limited maximum QO2 will be measured in the excised frog sartorius; Delta[ADP] will be measured under identical conditions, and compared with that predicted by the ADP trigger model. I have reported a large, progressive loss of mitochondrial CK during muscular dystrophy (MD). The shuttle model predicts that the time constant for QO2 in dystrophic muscle should be drastically increased thereby, perhaps compromising the ability of the cells to maintain their ATP store. This will be tested by measuring QO2 transients in isolated PLD muscles of normal and dystrophic chickens. The prediction will be further tested by measuring whole-body QO2 kinetics in human Duchenne MD patients during mild exercise.